The position of substructures and DNA sequences within the nucleus is highly organized, and this organization plays a role in regulating chromatin-dependent processes, such as gene expression. X chromosome inactivation is an experimentally amenable example of a phenomenon in which regulated changes in the location of specific DNA sequences is implicated in control of gene expression. In mammalian female cells, one X chromosome is silenced for dosage compensation of X-linked genes between males and females, and this process is essential for female survival. Here, we propose to investigate the molecular basis of the regulated changes in X chromosome nuclear organization that accompany X-inactivation. The insights gained are likely to be more generally applicable, since many of the factors that regulate X-inactivation also regulate gene expression in other contexts.